Deregulation of sebaceous gland, including enhanced sebocyte proliferation and sebum production, with abnormal differentiation and lipogenesis, is associated with several human diseases such as acne vulgaris, sebaceous hyperplasia, and sebaceous gland carcinoma, atopic dermatitis, seborrheic dermatitis and primary cicatricial alopecia. A mechanistic understanding of sebocyte proliferation and differentiation is important for developing novel therapeutic strategies to manage certain sebaceous gland disorder.
Acne vulgaris, the most common sebaceous gland diseases, is still a challenge to dermatologists since most medical and surgical therapies developed so far to treat acne vulgaris have relatively modest efficacy, possibly because of the inherent pathological complexity of the disease. Currently, topical retinoids, oral isotretinoin, and antimicrobials have been widely used as first-line therapies for acne since they can suppress sebaceous gland activity such as suppressing sebum secretion and reducing sebaceous lipogenesis or reduce the colonization of P. Acnes and its subsequent pro-inflammatory effects on comedogenesis. Unfortunately, these conventional therapies may not be effective against refractory acne, can lead to antibiotic resistance, or are associated with serious side effects. Although light and laser therapy and photodynamic therapy are growing in popularity as adjunctive treatments, it usually only shows short-term efficacy for inflammatory acne vulgaris. Therefore, their use as alternative acne treatments cannot be recommended until long-term studies are available that rule out a potential irreversible sebaceous gland destruction.
Galectin-12, a member of a β-galactoside-binding lectin family, contains two carbohydrate recognition domains (CRDs). Its mRNA contains five AU-rich motifs (AUUUA) which are known to confer instability to mRNA in the 3′-untranslated region, might therefore contributing to very restrict expression in adipocytes and peripheral blood leucocytes. (Yang, R. Y. et al., J Biol. Chem. 276:20252-20260 (2001)). Galectin-12 plays an important role in modulating adipogenesis by positively regulating expression of CCAAT enhancer-binding protein (C/EBP) and peroxisome proliferator-activated receptor (PPAR). (Yang, R. Y. et al., J Biol Chem. 279(28):29761-6. (2004) In addition, galectin-12 is specifically localized on lipid droplet and negatively regulates lipolysis and insulin sensitivity. (Yang, R. Y. et al., Proc Natl Acad Sci. 15; 108(46):18696-701(2011). Both C/EBPs and PPARs are also expressed in sebaceous gland cells and regulate sebocyte lipogenesis and differentiation. It has been demonstrated that galectin-12 is also expressed in human sebaceous glands and cultured sebocytes. (Harrison, W. J. et al., J Invest Dermatol. 127(6):1309-17. (2007)). However, its roles in sebocyte differentiation and the pathophysiology of sebaceous gland disorders remain to be elucidated.